Antibodies and cytokines independently protect against pneumonic plague.
Yersinia pestis causes pneumonic plague, an exceptionally virulent disease for which we lack a safe and effective vaccine. Antibodies specific for the Y. pestis F1 and LcrV proteins can protect mice against pulmonary Y. pestis infection. We demonstrate that neutralizing tumor necrosis factor-alpha (TNFalpha) and gamma-interferon (IFNgamma) abrogates this protection at sub-optimal levels of F1- or LcrV-specific antibody, but not at optimal levels. Moreover, we demonstrate that endogenous TNFalpha and IFNgamma confer measurable protection in the complete absence of protective antibodies. These findings indicate that antibodies and cytokines independently protect against pneumonic plague and suggest that surrogate assays for plague vaccine efficacy should consider both the level of vaccine-induced antibody and the capacity of vaccine recipients to produce TNFalpha and IFNgamma upon exposure to Y. pestis.
Kummer
Lawrence W
LW
Trudeau Institute, Saranac Lake, NY 12983, USA.
Szaba
Frank M
FM
Parent
Michelle A
MA
Adamovicz
Jeffrey J
JJ
Hill
Jim
J
Johnson
Lawrence L
LL
Smiley
Stephen T
ST
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology; D001426:Bacterial Proteins / Q000276:immunology; D016207:Cytokines / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D023381:Endpoint Determination; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010930:Plague / Q000382:microbiology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology / Q000627:therapeutic use*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use; D015010:Yersinia pestis / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D007106:Immune Sera; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; C086725:caf1 protein, Yersinia pestis; D007371:Interferon-gamma